title: Toward a therapeutic strategy for polyalanine expansions disorders: in vivo and in vitro models for drugs analysis.
abstract: Molecular pathogenesis of congenital disorders associated with polyalanine expansions has been investigated for several years. Despite different pathological hallmarks characterize each polyalanine disease, they share common features, mainly represented by aggregates containing the mutant proteins, usually mislocated inside the cellular compartments, along with ubiquitin and proteasome components. Recently, particular interest has been raised by investigations on molecules able to restore both correct localization and function of the expanded proteins. Here we report a list of drugs whose effects have been assayed both in in vitro and in vivo models of polyalanine disorders, such as the oculopharyingeal muscular dystrophy, congenital central hypoventilation syndrome, synpolydactyly and in cell and animal models carrying specific artificial mutations. In particular, we have reviewed, for each polyalanine mutant protein, the molecules tested, cellular models under investigation, drugs effects on aggregation and underlying mechanisms.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Di Zanni
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bachetti
mesh_terms: D000818:Animals; D019556:COS Cells; D018929:Cell Culture Techniques / Q000379:methods; D002522:Chlorocebus aethiops; D042622:DNA Repeat Expansion / Q000235:genetics*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D030342:Genetic Diseases, Inborn / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D010455:Peptides / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D010455:Peptides; C019529:polyalanine